PDHB

pyruvate dehydrogenase E1 subunit beta, the group of Pyruvate dehydrogenase complex

Basic information

Region (hg38): 3:58427630-58433857

Links

ENSG00000168291

∙ NCBI:5162 ∙ OMIM:179060 ∙ HGNC:8808 ∙ Uniprot:P11177 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

pyruvate dehydrogenase E1-beta deficiency (Strong), mode of inheritance: AR
pyruvate dehydrogenase E1-beta deficiency (Moderate), mode of inheritance: AR
pyruvate dehydrogenase E1-beta deficiency (Strong), mode of inheritance: AR
pyruvate dehydrogenase E1-beta deficiency (Supportive), mode of inheritance: AR
Leigh syndrome (Moderate), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Pyruvate dehydrogensae E1-beta deficiency	AR	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Biochemical; Neurologic	15138885; 21914562

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the PDHB gene.

Pyruvate_dehydrogenase_E1-beta_deficiency (323 variants)
Pyruvate_dehydrogenase_phosphatase_deficiency (28 variants)
not_provided (27 variants)
Inborn_genetic_diseases (22 variants)
not_specified (17 variants)
Pyruvate_dehydrogenase_complex_deficiency (16 variants)
PDHB-related_disorder (1 variants)
Seizure (1 variants)
See_cases (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the PDHB gene is commonly pathogenic or not. These statistics are base on transcript: NM_000000925.4. Only rare variants are included in the table.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUSVUS	Likely benignLB	BenignB	Sum
synonymous			5 clinvar	134 clinvar		139
missense	4 clinvar	7 clinvar	72 clinvar	4 clinvar		87
nonsense	3 clinvar	5 clinvar				8
start loss	1		1			2
frameshift	7 clinvar	7 clinvar				14
splice donor/acceptor (+/-2bp)	1 clinvar	5 clinvar	1 clinvar			7
Total	16	24	79	138	0

Highest pathogenic variant AF is 0.000237618

Loading clinvar variants...

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
PDHB	protein_coding	protein_coding	ENST00000302746	10	6228

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.152	0.847	125734	0	14	125748	0.0000557

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.57	139	202	0.690	0.00000975	2339
Missense in Polyphen		37	86.725	0.42664		1048
Synonymous	-0.853	74	65.2	1.13	0.00000305	703
Loss of Function	2.98	5	19.0	0.263	8.77e-7	232

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000579	0.0000579
Ashkenazi Jewish	0.0000992	0.0000992
East Asian	0.0000544	0.0000544
Finnish	0.000139	0.000139
European (Non-Finnish)	0.0000616	0.0000615
Middle Eastern	0.0000544	0.0000544
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

Function: FUNCTION: The pyruvate dehydrogenase complex catalyzes the overall conversion of pyruvate to acetyl-CoA and CO(2), and thereby links the glycolytic pathway to the tricarboxylic cycle. {ECO:0000269|PubMed:17474719, ECO:0000269|PubMed:19081061}.;
Disease: DISEASE: Pyruvate dehydrogenase E1-beta deficiency (PDHBD) [MIM:614111]: An enzymatic defect causing primary lactic acidosis in children. It is associated with a broad clinical spectrum ranging from fatal lactic acidosis in the newborn to chronic neurologic dysfunction with structural abnormalities in the central nervous system without systemic acidosis. {ECO:0000269|PubMed:15138885}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
Pathway: Citrate cycle (TCA cycle) - Homo sapiens (human);Pyruvate metabolism - Homo sapiens (human);Glycolysis / Gluconeogenesis - Homo sapiens (human);Central carbon metabolism in cancer - Homo sapiens (human);HIF-1 signaling pathway - Homo sapiens (human);Glucagon signaling pathway - Homo sapiens (human);Warburg Effect;Pyruvate Dehydrogenase Complex Deficiency;Transfer of Acetyl Groups into Mitochondria;The oncogenic action of Succinate;The oncogenic action of Fumarate;Primary hyperoxaluria II, PH2;Pyruvate kinase deficiency;Pyruvate dehydrogenase deficiency (E3);Pyruvate dehydrogenase deficiency (E2);2-ketoglutarate dehydrogenase complex deficiency;Mitochondrial complex II deficiency;Fumarase deficiency;Congenital lactic acidosis;Citric Acid Cycle;Leigh Syndrome;Glutaminolysis and Cancer;The oncogenic action of 2-hydroxyglutarate;Pyruvate Metabolism;The oncogenic action of L-2-hydroxyglutarate in Hydroxygluaricaciduria;The oncogenic action of D-2-hydroxyglutarate in Hydroxygluaricaciduria ;Pyruvate Decarboxylase E1 Component Deficiency (PDHE1 Deficiency);Hereditary Leiomyomatosis and Renal Cell Carcinoma Pathway;Glycolysis and Gluconeogenesis;Signal Transduction;Regulation of pyruvate dehydrogenase (PDH) complex;Pyruvate metabolism;Pyruvate metabolism and Citric Acid (TCA) cycle;Metabolism of amino acids and derivatives;The citric acid (TCA) cycle and respiratory electron transport;Glycolysis and Gluconeogenesis;Metabolism;pyruvate decarboxylation to acetyl CoA;Glyoxylate metabolism and glycine degradation;Pyruvate metabolism;Signaling by Retinoic Acid;Signaling by Nuclear Receptors;superpathway of conversion of glucose to acetyl CoA and entry into the TCA cycle (Consensus)

Recessive Scores

pRec: 0.447

Intolerance Scores

loftool: 0.124
rvis_EVS: -0.41
rvis_percentile_EVS: 26.23

Haploinsufficiency Scores

pHI: 0.393
hipred: Y
hipred_score: 0.685
ghis: 0.658

Essentials

essential_gene_CRISPR: N
essential_gene_CRISPR2: N
essential_gene_gene_trap: N
gene_indispensability_pred: E
gene_indispensability_score: 0.990

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

Gene name: Pdhb
Phenotype

Zebrafish Information Network

Gene name: pdhb
Affected structure: amacrine cell
Phenotype tag: abnormal
Phenotype quality: decreased amount

Gene ontology

Biological process: glucose metabolic process;acetyl-CoA biosynthetic process from pyruvate;tricarboxylic acid cycle;mitochondrial acetyl-CoA biosynthetic process from pyruvate
Cellular component: nucleus;nucleoplasm;mitochondrion;mitochondrial matrix;pyruvate dehydrogenase complex
Molecular function: pyruvate dehydrogenase activity;pyruvate dehydrogenase (acetyl-transferring) activity;protein binding;pyruvate dehydrogenase (NAD+) activity